Functional Upregulation of TRPM3 Channels Contributes to Acute Pancreatitis-associated Pain and Inflammation.

Transient receptor potential melastatin M3 (TRPM3) channels have been recognized as a pain transducer in dorsal root ganglion (DRG) neurons in recent years. TRPM3 activation initiates neurogenic inflammation and is required for the development of inflammatory hyperalgesia. We aimed to evaluate the role of TRPM3 in pancreas sensory afferents in pancreatic nociception, neurogenic inflammation, and acute pancreatitis (AP)-associated pain. AP was induced by intraperitoneal (i.p.) injection of L-arginine in rats. TRPM3 expression in pancreatic DRG neurons, spontaneous or mechanical-stimulation-evoked pain behaviors, and the extent of inflammation were evaluated. We found that TRPM3 channels were expressed on pancreatic primary afferent nerve terminals containing calcitonin gene-related peptide (CGRP). Activation of TRPM3 in the pancreas by injection of its specific agonist CIM0216 (10 µM) induced pain, CGRP and substance P release, and neurogenic inflammation, as evidenced by edema, plasma extravasation, and inflammatory cell accumulation in the pancreas. Increased TRPM3 functional expression was detected in pancreatic DRG neurons from AP rats, and blocking TRPM3 activity with its antagonist (Primidone, 5 mg/kg, i.p.) attenuated AP-associated pain behaviors and pancreatic inflammation. Pre-incubation of pancreatic DRG neurons with nerve growth factor (NGF) enhanced the increase in intracellular Ca2+ induced by the TRPM3 agonist (CIM0216, 1 µM). Our findings indicate that, in addition to TRPV1 and TRPA1 channels, TRPM3 is another pain channel that has a critical role in pancreatic nociception, neurogenic inflammation, and AP-associated pain behaviors. TRPM3 may be a promising pharmaceutical target for AP pain treatment.

Deciphering the immune-metabolic nexus in sepsis: a single-cell sequencing analysis of neutrophil heterogeneity and risk stratification.

Background: Metabolic dysregulation following sepsis can significantly compromise patient prognosis by altering immune-inflammatory responses. Despite its clinical relevance, the exact mechanisms of this perturbation are not yet fully understood. Methods: Single-cell RNA sequencing (scRNA-seq) was utilized to map the immune cell landscape and its association with metabolic pathways during sepsis. This study employed cell-cell interaction and phenotype profiling from scRNA-seq data, along with pseudotime trajectory analysis, to investigate neutrophil differentiation and heterogeneity. By integrating scRNA-seq with Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, key genes were identified. These genes were used to develop and validate a risk score model and nomogram, with their efficacy confirmed through Receiver Operating Characteristic (ROC) curve analysis. The model's practicality was further reinforced through enrichment and immune characteristic studies based on the risk score and in vivo validation of a critical gene associated with sepsis. Results: The complex immune landscape and neutrophil roles in metabolic disturbances during sepsis were elucidated by our in-depth scRNA-seq analysis. Pronounced neutrophil interactions with diverse cell types were revealed in the analysis of intercellular communication, highlighting pathways that differentiate between proximal and core regions within atherosclerotic plaques. Insight into the evolution of neutrophil subpopulations and their differentiation within the plaque milieu was provided by pseudotime trajectory mappings. Diagnostic markers were identified with the assistance of machine learning, resulting in the discovery of PIM1, HIST1H1C, and IGSF6. The identification of these markers culminated in the development of the risk score model, which demonstrated remarkable precision in sepsis prognosis. The model's capability to categorize patient profiles based on immune characteristics was confirmed, particularly in identifying individuals at high risk with suppressed immune cell activity and inflammatory responses. The role of PIM1 in modulating the immune-inflammatory response during sepsis was further confirmed through experimental validation, suggesting its potential as a therapeutic target. Conclusion: The understanding of sepsis immunopathology is improved by this research, and new avenues are opened for novel prognostic and therapeutic approaches.

Activation of Piezo1 or TRPV2 channels inhibits human ureteral contractions via NO release from the mucosa.

We aimed to investigate the expression and motor modulatory roles of several mechano-sensitive channels (MSCs) in human ureter. Human proximal ureters were obtained from eighty patients subjected to nephrectomy. Expression of MSCs at mRNA, protein and functional levels were examined. Contractions of longitudinal ureter strips were recorded in organ bath. A fluorescent probe Diaminofluoresceins was used to measure nitric oxide (NO). RT-PCR analyses revealed predominant expression of Piezo1 and TRPV2 mRNA in intact ureter and mucosa. Immunofluorescence assays indicate proteins of MSCs (Piezo1/Piezo2, TRPV2 and TRPV4) were mainly distributed in the urothelium. Ca2+ imaging confirmed functional expression of TRPV2, TRPV4 and Piezo1 in cultured urothelial cells. Specific agonists of Piezo1 (Yoda1, 3-300 µM) and TRPV2 (cannabidiol, 3-300 µM) attenuated the frequency of ureteral contractions in a dose-dependent manner while the TRPV4 agonist GSK1016790A (100 nM-1 µM) exerted no effect. The inhibitory effects of Piezo1 and TRPV2 agonists were significantly blocked by the selective antagonists (Dooku 1 for Piezo1, Tranilast for TRPV2), removal of the mucosa, and pretreatment with NO synthase inhibitor L-NAME (10 µM). Yoda1 (30 µM) and cannabidiol (50 µM) increased production of NO in cultured urothelial cells. Our results suggest that activation of Piezo1 or TRPV2 evokes NO production and release from mucosa that may mediate mechanical stimulus-induced reduction of ureter contractions. Our findings support the idea that targeting Piezo1 and TRPV2 channels may be a promising pharmacological strategy for ureter stone passage or colic pain relief.

Enhancing higher-order modal response in multifrequency atomic force microscopy with a coupled cantilever system.

Multifrequency atomic force microscopy (AFM) utilizes the multimode operation of cantilevers to achieve rapid high-resolution imaging and extract multiple properties. However, the higher-order modal response of traditional rectangular cantilever is weaker in air, which affects the sensitivity of multifrequency AFM detection. To address this issue, we previously proposed a bridge/cantilever coupled system model to enhance the higher-order modal response of the cantilever. This model is simpler and less costly than other enhancement methods, making it easier to be widely used. However, previous studies were limited to theoretical analysis and preliminary simulations regarding ideal conditions. In this paper, we undertake a more comprehensive investigation of the coupled system, taking into account the influence of probe and excitation surface sizes on the modal response. To facilitate the exploration of the effectiveness and optimal conditions for the coupled system in practical applications, a macroscale experimental platform is established. By conducting finite element analysis and experiments, we compare the performance of the coupled system with that of traditional cantilevers and quantify the enhancement in higher-order modal response. Also, the optimal conditions for the enhancement of macroscale cantilever modal response are explored. Additionally, we also supplement the characteristics of this model, including increasing the modal frequency of the original cantilever and generating additional resonance peaks, demonstrating the significant potential of the coupled system in various fields of AFM.

HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway.

BACKGROUND: Heart failure (HF) is a heterogeneous syndrome that affects millions worldwide, resulting in substantial health and economic burdens. However, the molecular mechanism of HF pathogenesis remains unclear. METHODS: HF-related key genes were screened by a bioinformatics approach.The impacts of HAPLN1 knockdown on Angiotensin II (Ang II)-induced AC16 cells were assessed through a series of cell function experiments. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of oxidative stress and apoptosis-related factors. The HF rat model was induced by subcutaneous injection isoprenaline and histopathologic changes in the cardiac tissue were assessed by hematoxylin and eosin (HE) staining and echocardiographic index. Downstream pathways regulated by HAPLN1 was predicted through bioinformatics and then confirmed in vivo and in vitro by western blot. RESULTS: Six hub genes were screened, of which HAPLN1, FMOD, NPPB, NPPA, and COMP were overexpressed, whereas NPPC was downregulated in HF. Further research found that silencing HAPLN1 promoted cell viability and reduced apoptosis in Ang II-induced AC16 cells. HAPLN1 knockdown promoted left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), while decreasing left ventricular end-systolic volume (LVESV) in the HF rat model. HAPLN1 knockdown promoted the levels of GSH and suppressed the levels of MDA, LDH, TNF-α, and IL-6. Mechanistically, silencing HAPLN1 activated the PKA pathway, which were confirmed both in vivo and in vitro. CONCLUSION: HAPLN1 knockdown inhibited the progression of HF by activating the PKA pathway, which may provide novel perspectives on the management of HF.

Adaptive under-sampling strategy for fast imaging in compressive sensing-based atomic force microscopy.

Compressive sensing (CS) can reconstruct the rest information almost without distortion by advanced computational algorithm, which significantly simplifies the process of atomic force microscope (AFM) scanning with high imaging quality. In common CS-AFM, the partial measurements randomly come from the whole region to be measured, which easily leads to detail loss and poor image quality in regions of interest (ROIs). Consequently, important microscopic phenomena are missed probably. In this paper, we developed an adaptive under-sampling strategy for CS-AFM to optimize the process of sampling. Under a certain under-sampling ratio, the weight coefficient of ROIs and regions of base (ROBs) were set to control the distribution of under-sampling points and corresponding measurement matrix. A series of simulations were completed to demonstrate the relationship between the weight coefficient of ROIs and image quality. After that, we verified the effectiveness of the method on our homemade AFM. Through a lot of simulations and experiments, we demonstrated how the proposed method optimized the sampling process of CS-AFM, which speeded up the process of AFM imaging with high quality.

Piezo2 Channel Upregulation is Involved in Mechanical Allodynia in CYP-Induced Cystitis Rats.

Mechanical sensing Piezo2 channel in primary sensory neurons has been shown contribute to mechanical allodynia in somatic chronic pain conditions. Interstitial cystitis (IC)-associated pain is often triggered by bladder filling, a presentation that mimics the mechanical allodynia. In the present study, we aimed to examine the involvement of sensory Piezo2 channel in IC-associated mechanical allodynia using a commonly employed cyclophosphamide (CYP)-induced IC model rat. Piezo2 channels in dorsal root ganglia (DRGs) was knocked down by intrathecal injections of Piezo2 anti-sense oligodeoxynucleotides (ODNs) in CYP-induced cystitis rats, and mechanical stimulation-evoked referred bladder pain was measured in the lower abdomen overlying the bladder using von Frey filaments. Piezo2 expression at the mRNA, protein, and functional levels in DRG neurons innervating the bladder was detected by RNA-fluorescence in situ hybridization, western blotting, immunofluorescence, and Ca2+ imaging, respectively. We found that Piezo2 channels were expressed on most (> 90%) of the bladder primary afferents, including afferents that express CGRP, TRPV1 and stained with isolectin B4. CYP-induced cystitis was associated with Piezo2 upregulation in bladder afferent neurons at the mRNA, protein, and functional levels. Knockdown of Piezo2 expression in DRG neurons significantly suppressed mechanical stimulation-evoked referred bladder pain as well as bladder hyperactivity in CYP rats compared to CYP rats treated with mismatched ODNs. Our results suggest upregulation of Piezo2 channels is involved in the development of bladder mechanical allodynia and bladder hyperactivity in CYP-induced cystitis. Targeting Piezo2 might be an attractive therapeutic approach for IC-related bladder pain.

Equivalent Electromechanical Model for Quartz Tuning Fork Used in Atomic Force Microscopy.

Quartz tuning forks (QTFs) are self-sensing and possess a high quality factor, allowing them to be used as probes for atomic force microscopes (AFMs) for which they offer nano-scale resolution of sample images. Since recent work has revealed that utilizing higher-order modes of QTFs can offer better resolution of AFM images and more information on samples, it is necessary to understand the relationship between the vibration characteristics of the first two symmetric eigenmodes of quartz-based probes. In this paper, a model that combines the mechanical and electrical characteristics of the first two symmetric eigenmodes of a QTF is presented. Firstly, the relationships between the resonant frequency, amplitude, and quality factor between the first two symmetric eigenmodes are theoretically derived. Then, a finite element analysis is conducted to estimate the dynamic behaviors of the analyzed QTF. Finally, experimental tests are executed to verify the validity of the proposed model. The results indicate that the proposed model can accurately describe the dynamic properties of a QTF in the first two symmetric eigenmodes either under electrical or mechanical excitation, which will provide a reference for the description of the relationship between the electrical and mechanical responses of the QTF probe in the first two symmetric eigenmodes as well as the optimization of higher modal responses of the QTF sensor.

Neuro-protective effect of Linalool against spinal cord injury in rats and the mechanism involved / Efecto neuroprotector del Linalool contra la lesión de la médula espinal en ratas y el mecanismo involucrado

The current study was conducted to determine the neuroprotective role and mechanism of action of Linalool (LIN) in SCI. The SCI in Sprague-Dawley (SD) rats was induced by weight-drop contusion model. Results of the suggested that LIN showed improvement in the locomotor function of SCI rats in a BBB scoring analysis. It was found in agreement with histopathological analysis of spinal cord tissue where LIN improves the neuronal architecture of spinal cord tissues, and protect neurons from degeneration. It also reduces oxidative stress via modulating endogenous antioxidants (MDA, SOD, and GSH) and inhibits the generation of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6). In western blot analysis, LIN showed dose-dependent reduction of expression of toll-like receptor (TLR-4) and nuclear factor-kappa B (NF-ĸB). Our study demonstrated that administration of Linalool alleviated spinal cord injury via anti-inflammatory and antioxidant activities in spinal cord tissues possibly due to inhibition of TLR4/NF-κB activation.

El estudio actual se realizó para determinar el papel neuroprotector y el mecanismo de acción de Linalool (LIN) en SCI. La LIN en ratas Sprague-Dawley (SD) se indujo mediante el modelo de contusión de caída de peso. Los resultados sugirieron que LIN mostró una mejora en la función locomotora de ratas SCI en un análisis de puntuación BBB. De acuerdo con el análisis histopatológico del tejido de la médula espinal se encontró que LIN mejora la arquitectura neuronal de los tejidos de la médula espinal y protege a las neuronas de la degeneración. También reduce el estrés oxidativo mediante la modulación de antioxidantes endógenos (MDA, SOD y GSH) e inhibe la generación de citocinas proinflamatorias (TNF-α, IL-1ß e IL-6). En el análisis de Western blot, LIN mostró una reducción dependiente de la dosis de la expresión del receptor tipo toll (TLR-4) y el factor nuclear kappa B (NF-ĸB). Nuestro estudio demostró que la administración de Linalool alivió la lesión de la médula espinal a través de actividades antiinflamatorias y antioxidantes en los tejidos de la médula espinal, posiblemente debido a la inhibición de la activación de TLR4/NF-κB.

Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3ß/snail pathway.

BACKGROUND: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate cancer. METHODS: The expression of DANCR, microRNA (miR)-185-5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate cancer tissues and normal tissues, five prostate cancer cell lines and one epithelial cell line was assessed by a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4-2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial-mesenchymal transition (EMT) protein expression were tested via cell counting kit-8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR-185-5p and LASP1 were verified by a dual-luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4-2 cells. The involvement of the signaling pathway was examined using a p-FAK inhibitor. RESULTS: DANCR and LASP1 expression was enhanced, whereas miR-185-5p expression was diminished in prostate cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1-S transition and expression of EMT proteins of the transfected PC3 and C4-2 cells. DANCR sponged miR-185-5p to upregulate LASP1 expression. DANCR-miR-185-5p-LASP1 axis activates the FAK/PI3K/AKT/GSK3ß/Snail pathway to promote the malignant properties of PC3 and C4-2 cells. CONCLUSIONS: These findings suggest that DANCR exerts oncogenic roles in prostate cancer via the miR-185-5p/LASP1 axis activating the FAK/PI3K/AKT/GSK3ß/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate cancer.

Real-time transrectal ultrasound-guided seminal vesiculoscopy for the treatment of patients with persistent hematospermia: A single-center, prospective, observational study.

This study aimed to describe endoscopic anatomy of the seminal tract and summarize our experience of transutricular seminal vesiculoscopy (TSV) guided by real-time transrectal ultrasonography (TRUS) in managing persistent hematospermia. A total of 281 consecutive patients with persistent hematospermia who underwent TSV with or without real-time TRUS were enrolled in this single-center, prospective, observational study. The median follow-up period was 36.5 (range: 8.0-97.5) months. TSV was successfully performed in 272 (96.8%) patients. The approach of a 4.5/6 F rigid vesiculoscope entering the seminal tract was categorized into four types on the basis of endoscopic presentation of the ejaculatory duct orifice and verumontanum. Seven (2.6%), 74 (27.2%), 64 (23.5%), and 127 (46.7%) patients had Types I (through the ejaculatory duct in the urethra), II (through the ejaculatory duct in the prostatic utricle), III (transutricular fenestration through a thin membrane), and IV (real-time transrectal ultrasound-guided transutricular fenestration) approach, respectively. In patients who successfully underwent surgery, bleeding occurred in the seminal vesicle in 249 (91.5%) patients. Seminal vesiculitis, calculus in the prostatic utricle, calculus in the ejaculatory duct, calculus in the seminal vesicle, prostatic utricle cysts, and seminal vesicle cysts were observed in 213 (78.3%), 96 (35.3%), 22 (8.1%), 81 (29.8%), 25 (9.2%), and 11 (4.0%) patients, respectively. Hematospermia was alleviated or disappeared in 244 (89.7%) patients 12 months after surgery. Fifteen patients had recurrent hematospermia, and the median time to recurrence was 7.5 (range: 2.0-18.5) months. TSV guided by TRUS may contribute to successful postoperative outcomes in managing persistent hematospermia.

Systematically transplanted human gingiva-derived mesenchymal stem cells regulate lipid metabolism and inflammation in hyperlipidemic mice with periodontitis.

Gingiva-derived mesenchymal stem cells (GMSCs) have been the focus of extensive research due to their numerous distinct properties, including their homing to injury sites and their contribution to tissue regeneration. However, the role of transplanted GMSCs in the regulation of lipid metabolism and inflammation in hyperlipidemic mice with periodontitis has not been demonstrated. In the present study, apolipoprotein E-deficient (ApoE-/-) mice were used to establish a hyperlipidemia model with periodontitis and divided into two groups: Group B and Group C (n=20 per group), and wild-type C57BL/6J mice without any treatment were assigned to Group A (n=20). Animals in Group C were then injected with human GMSCs through the tail vein and animals in Group B were injected with α-MEM as control. Animals were sacrificed at indicated time points. Serum was collected to determine the lipids and inflammatory cytokines. Liver samples were collected to estimate lipid-associated gene expression. Morphometric and histological analyses were performed to maxillaries. The results demonstrated that the delivery of GMSCs led to a significant decrease in triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL), interleukin (IL)-6, tumor necrosis factor (TNF)-α, alveolar bone loss (ABL), and sterol regulatory element binding protein-1c (SREBP-1c) mRNA, and a significant increase in high density lipoprotein cholesterol (HDL), IL-10 and peroxisome proliferator-activated receptor α (PPARα) mRNA in Group C compared to Group B. Histological examination showed increased formation of new bone and higher alveolar bone height in Group C. Systematically transplanted GFP-positive cells were detected through both fluorescence microscope observation and immunohistochemical staining in the periodontal tissues. Overall, systematically transplanted GMSCs attenuated the hyperlipidemia and inflammatory responses in hyperlipidemic mice with periodontitis, and improved periodontal tissue regeneration.

Dendrite-free deposition on lithium anode toward long-life and high-stable Li//graphite dual-ion battery.

Metallic lithium protection plays a crucial role on improving the electrochemical properties of Li-anode-based batteries. Herein, for an advanced Li//graphite dual-ion battery, constructing a robust and conductive film of carbon nanofibers on a Li anode effectively achieves dendrite-free Li growth and hence significantly enhances the long-life cyclic stability.

Identification of prognostic biomarkers of prostate cancer with long non-coding RNA-mediated competitive endogenous RNA network.

Prostate cancer (PCa) is the second most frequently diagnosed male cancer, and no treatments exist for effective inhibition of metastatic spread of PCa. Long non-coding RNA (lncRNA) plays key roles in pathogenesis and development of various cancers through competing with endogenous RNAs (ceRNAs), but at present research on lncRNA functions in PCa is still very limited. Hence, this aspect was investigated using bioinformatics methods. Firstly, the functional lncRNA-mediated ceRNA network associated with PCa was constructed by the multi-step computational approach. Then the cytoscape software was used to analyze the node degree and betweenness centrality (BC) value of lncRNAs and mRNAs in the interaction. Finally, the lncRNAs were screened in the central region of the network by the node degree and BC value, and the functional enrichment of mRNAs was evaluated with the Gene Ontology (GO) database. In our results, LINC00476, MALAT1, SNHG11, LINC00649, and ILF3-AS1 are the lncRNAs which have the most nodes and higher BC values and considered as prognostic markers in PCa. GO analysis suggested that the function of screened lncRNAs was obviously focused on intracellular receptor signaling pathway, which indicated these lncRNAs might be potential biomarkers for diagnosis, evaluation and gene-targeted therapy of PCa.

The treatment of systematically transplanted gingival mesenchymal stem cells in periodontitis in mice.

Cell-based tissue engineering is a promising alternative for periodontal regeneration as current therapies fail to reconstitute tissue damage caused by periodontitis. As newly identified postnatal stem cells, gingiva-derived mesenchymal stem cells (GMSCs) have been focused on for isolation and expansion in vitro of cells with multi-differentiation potential and immunomodulatory capacities. It has been demonstrated that systemically delivered GMSCs can home to the mandibular bone defect sites and promote bone regeneration. However, the role of transplanted GMSCs in the treatment of periodontitis has not been reported. In the present study, GMSCs were transplanted into C57BL/6J mice with periodontitis via the tail vein to investigate the contribution of GMSCs to periodontal tissue regeneration. Results demonstrated that the alveolar bone heights of mice with transplanted GMSCs were significantly increased compared with the control groups and GMSCs were detected in newly formed periodontal ligament and alveolar bone. The results of the present study implied that systemically transplanted GMSCs could home to periodontal injury sites and promote periodontal tissue regeneration.

An experimental hyperlipidemia model with periodontitis in mice.

PURPOSE: In many animal models and clinical trials, the relationship between periodontitis and hyperlipidemia is bidirectional and interlinked. In this study, an experimental hyperlipidemia model with periodontitis in mice is introduced. METHODS: C57BL/6J mice were assigned into group A and B and Apolipoprotein E-deficient (ApoE-/-) mice into group C. After 4 weeks of a high fat diet (HFD), group B and C were ligated on the maxillary second molar tooth, and mice were sacrificed after 8 weeks of the HFD. Levels of lipids, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α in serum after 0, 4, and 8 weeks were determined. Alveolar bone loss (ABL) was assessed under stereomicroscope. Maxillary bones and atherosclerotic lesion area in the aorta were collected for hematoxylin and eosin (HE) staining. RESULTS: After feeding with a HFD for 4 weeks, group C demonstrated dramatic increases in serum lipid levels. The ABL and levels of IL-6, IL-10, and TNF-α in group C was significantly higher than those of group A and B (P<0.05). Atherosclerotic lesions were observed in group C. CONCLUSIONS: These data demonstrate that an experimental hyperlipidemia model with periodontitis in mice is successfully established by ligation in ApoE-/- mice. This method is economical and time saving, and worthy of more general application.

Application of pulsed arterial resuscitation in a rabbit model of hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is characterized by tissue hypoperfusion caused by a sharp reduction in the effective circulating volume of blood. The key to successful resuscitation lies in eliminating the shock as soon as possible while simultaneously restoring blood perfusion to vital organs. We present the applicability of pulsed arterial blood reinfusion for resuscitation of hemorrhagic shock. METHODS: Sixty rabbits were randomly assigned to resuscitation and control groups. A rabbit hemorrhagic shock model was developed by bloodletting from the carotid artery. The dynamic changes in blood pressure, urine output, blood lactate, and other indicators were measured. RESULTS: Compared with the control group, the mean arterial pressure (MAP), pulse pressure, and urine output were significantly higher in the resuscitation group at 60 min (MAP: 83.67±3.90 vs. 38.19±3.50 mmHg, p<0.001; pulse difference: 16.46±2.21 vs. 10.27±2.99 mmHg, p<0.001; urine output: 3.68±0.74 vs. 0.10±0.05 mL·kg-1·min-1, p<0.001), whereas the serum lactate level was significantly lower (3.82±0.50 vs. 6.49±0.61 mmol/L, p<0.001). In addition, the resuscitation group had a significantly higher lactate clearance rate (30 min: 0.26%±0.11% vs. 0.25%±0.14%, p<0.001; 60 min: 0.30%±0.09% vs. 0.67%±0.26%, p<0.001) than the control group. CONCLUSION: Pulsed arterial resuscitation might be useful for emergency treatment of hemorrhagic shock.

Transcutaneous electrical stimulation of somatic afferent nerves in the foot relieved symptoms related to postoperative bladder spasms.

BACKGROUND: Bladder spasm is a common side effect of urological surgery. Main treatment modalities include opioids or anticholinergic medication; however, bladder spasms still occur even after these interventions. Recent studies indicate that transcutaneous stimulation of the foot can result in 50% increase in bladder capacity in healthy adults, and inhibit bladder detrusor overactivity in spinal cord injured patients. In this study, we examined the effects of transcutaneous electrical stimulation of the foot on bladder spasms related symptoms. METHODS: Sixty-six male patients who underwent prostate or bladder surgeries due to benign prostatic hyperplasia or bladder diseases were randomly divided into two groups: the control group (n = 36) and the treatment group (n = 30). The control group received the routine postoperative care. The treatment group received daily transcutaneous electrical stimulation of the foot during 3 days after surgery; each time lasted for 60 min. All patients were evaluated by the Visual Analogue Scale for pain sensation, frequency of bladder spasm episodes, and a total score of bladder spasms symptoms. RESULTS: In the control group, the patients with bladder surgery had a higher Visual Analogue Scale score than patients with prostate surgery (P = 0.024). In both treatment and control groups, the Visual Analogue Scale score, spasm frequency, and total score of bladder spasm symptoms decreased from day 1 to day 3 (P <0.001). The Visual Analogue Scale score at day 2, total score of bladder spasm symptoms at day 2 and day 3 were significantly lower in the treatment group than in the control group (P <0.05). CONCLUSION: These results provided preliminary evidence suggesting beneficial effects of stimulating somatic afferent nerves in the foot on postoperative bladder spasms. TRIAL REGISTRATION: The study was registered with Chinese Clinical Trial Registry on June 13 2016 ( http://www.chictr.org.cn/ ) (Identifier: ChiCTR-INR-16008635).

The application of laparoscopic Doppler ultrasound during laparoscopic varicocelectomy in infertile men.

The aim of this study is to evaluate the benefits of laparoscopic Doppler ultrasound (LDU) application during laparoscopic varicocelectomy (LV), and to compare the surgical outcomes and complications between LDU-assisted LV (LDU-LV) and conventional LV for infertile patients with varicoceles; 147 infertile patients were randomly divided into two groups. Operative and postoperative parameters, semen parameters, and the pregnancy rate were compared. There were no differences in baseline demographics. The operative time was significantly longer in LDU-LV group than LV group. The incidence of postoperative hydrocele was 1.4% (1/72) in LDU-LV group versus 10.7% (8/75) in LV group, which showed a significant difference (P < 0.05). However, other surgical outcomes, such as postoperative hospital stay, postoperative recurrence, and testicular atrophy, were similar between the two groups. Sperm concentration and sperm motility were significantly increased in both groups at 3, 6, and 12 months after surgery (P < 0.01), and they were higher in LDU-LV than LV group in 12 months after surgery (34.21 ± 6.36 vs 29.99 ± 6.04 for concentration, P < 0.05; 40.72 ± 8.12 vs 37.31 ± 6.12 for motility, P < 0.05). Sperm morphology was comparable between the two groups. The pregnancy rate showed no significant difference (44.4% of the LDU-LV vs 37.3% of the LV, P > 0.05). In conclusion, compared with LV, LDU-LV could safely and effectively ligate all spermatic veins and preserve spermatic arteries without leading to high varicocele recurrence and postoperative hydrocele. Given the benefits that sperm counts as well as sperm motility favoring LDU-LV, we recommend that LDU should be routinely used as an effective tool to improve outcomes and safety of laparoscopic varicocelectomy.

Suppression of LASP-1 attenuates the carcinogenesis of prostatic cancer cell lines: Key role of the NF-κB pathway.

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among males worldwide and causes a considerable number of deaths each year. One of the newly explored targets for the development of therapies against PCa is LIM and SH3 protein 1 (LASP-1). In the present study, the function of LASP-1 in the oncogenesis and metastasis of PCa was investigated using a series of in vitro experiments. Moreover, the mechanism through which LASP-1 exerted its effect on the carcinogenesis of PCa was also explored. The expression levels of LASP-1 in clinical PCa specimens were determined both at the mRNA and protein levels. Afterwards, the activity of LASP-1 in human PCa cell lines PC3 and DU145 was inhibited using a short hairpin RNA (shRNA) interfering method. The effects of LASP-1 knockdown on the cell growth, apoptosis, cell cycle distribution, migration and invasion were assessed. It was demonstrated that the expression of LASP-1 was significantly higher in the clinical PCa tissues than the level in the corresponding para-carcinoma tissues. Following the knockdown of the LASP-1 gene in human PCa cell lines, the viability, migration and invasion of the cancer cells were decreased. It was also demonstrated that the change in the cell viability and motile ability were associated with an induction of cell apoptosis and G1 phase cell cycle arrest. Based on the results of the detection of the expression of NF-κB-related factors, it was indicated that LASP-1 may affect the carcinogenesis of PCa through a NF-κB inhibition-dependent manner. Although the detailed explanation of the mechanism of LASP-1 in the carcinogenesis of PCa requires further elucidation, the present study highlights the potential of LASP-1 as a promising therapeutic target to ameliorate the oncogenesis and metastasis of PCa.